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Mitochondria specific highly cytoselective iridium(iii)-Cp* dipyridophenazine (dppz) complexes as cancer cell imaging
Nilmadhab Roy1, Utsav Sen, Shreya Ray Chaudhuri
1Department of Chemistry, School of Advanced Sciences, VIT, Vellore-632014, Tamil Nadu, India. priyankar.paira@vit.ac.in.
Abstract:
Cancer is the most incurable pernicious disease to date after cardiovascular disease with an immeasurable rate of mortality. However, effective cancer medication and therapy are still castles in the sky to researchers. Therefore, in search of an appropriate strategy to annihilate cancer, we have designed a set of Ir(iii)-Cp* dipyridophenazine complexes as luminescent anticancer agents combining the cancer inhibiting potency of the planar dipyridophenazine (dppz) moiety through DNA interaction and mitochondrial dysfunction with the wonderful photoluminescence ability and target specificity of iridium metal. Hence, with the synergy of these dual aspects in the same system, we have aspired to emphasize the theranostic approach of cancer treatment in the present study by preparing effective, aqueous-soluble, mitochondria-targeting, highly cytoselective, luminescent, cancer cell-permeable scaffolds, enabling diagnosis as well as the healing of cancer cells in the body. Here, the presence of the cyclopentadienyl (Cp*) moiety in association with the fluorine group has boosted the lipophilic character of the complexes. Also, the cytotoxicity screening of the prepared Cp*Ir(iii)-dipyridophenazine complexes (IrL1-IrL7) against colorectal adenocarcinoma cells (Caco-2) and human epitheloid cervix carcinoma cells (HeLa) clearly identified them as potential anticancer agents and imaging studies unveiled their superb cellular imaging properties. Among them, the complex [(η5-Cp*)IrCl(11-fluorodipyrido[3,2-a:2',3'-c]phenazine)] (IrL6) achieved the best cytoselectivity. However, the superiority of the anticancer potency of [(η5-Cp*)IrCl(benzo[i]dipyrido[3,2-a:2',3'-c]phenazine)] (IrL3) was also corroborated by its activity against the most aggressive colorectal carcinoma cell line (HT-29), whereas (η5-Cp*)IrCl(11-(trifluoromethyl)dipyrido[3,2-a:2',3'-c]phenazine (IrL5) came into the limelight as the best theranostic agent as it showed remarkable cytoselectivity as well as significant cellular imaging properties, endowing it with the highest quantum yield value among all the complexes.
Insights
Researchers developed novel iridium(III) complexes for cancer theranostics. These luminescent agents target cancer cells via DNA interaction and mitochondrial dysfunction, offering dual diagnostic and therapeutic benefits for improved cancer treatment strategies.
Area of Science:
- Inorganic Chemistry
- Medicinal Chemistry
- Biochemistry
Background:
- Cancer remains a leading cause of mortality, with unmet needs for effective treatments.
- Current cancer therapies face limitations in efficacy and specificity.
- Developing novel agents for targeted cancer treatment and diagnosis is crucial.
Purpose of the Study:
- To design and synthesize novel iridium(III)-cyclopenta-dienyl (Cp*) dipyridophenazine (dppz) complexes as luminescent anticancer agents.
- To explore the theranostic potential of these complexes, combining anticancer activity with imaging capabilities.
- To evaluate the efficacy, cellular uptake, and targeting of these complexes in cancer cells.
Main Methods:
- Synthesis of a series of Cp*Ir(iii)-dipyridophenazine complexes (IrL1-IrL7).
- Cytotoxicity screening against colorectal adenocarcinoma (Caco-2) and human epitheloid cervix carcinoma (HeLa) cell lines.
- Cellular imaging studies to assess localization and photoluminescence properties.
- Evaluation of DNA interaction and mitochondrial dysfunction mechanisms.
Main Results:
- The synthesized Cp*Ir(iii)-dipyridophenazine complexes exhibited significant anticancer activity and potent luminescent properties.
- Complex IrL6 showed the highest cytoselectivity, while IrL3 demonstrated superior anticancer potency against aggressive colorectal cancer cells (HT-29).
- Complex IrL5 emerged as the leading theranostic agent, displaying remarkable cytoselectivity, significant cellular imaging capabilities, and the highest quantum yield.
Conclusions:
- Cp*Ir(iii)-dipyridophenazine complexes represent promising candidates for dual-action cancer theranostics.
- The synergistic combination of iridium's photoluminescence and dppz's anticancer mechanisms offers a novel therapeutic strategy.
- Further investigation into these complexes could lead to advanced imaging and treatment modalities for cancer.
